This application for a FIRST award is focused on the genetic epidemiology of schizophrenia. Though a genetic etiology for schizophrenia is accepted, the mode of inheritance and the nature of the disease gene/s are unknown. In order to identify such genes without assuming the mode of inheritance a case-control association study is proposed. The study will investigate proposed associations with schizophrenia at two loci: (i) a positive association at the dopamine D3 receptor gene (D3RG) locus, (ii) a negative association at the HLA DQB1 gene locus. These hypotheses are based on the applicant's preliminary studies, which suggest associations among individuals of African-American ethnicity. Therefore, the probands will be African-Americans with a diagnosis of schizophrenia (DSM IIlR criteria, n= 150). The distribution of alleles of D3RG and HLA DQB 1 among the probands will be compared with two groups of controls: (i) a hypothetical group composed of alleles not transmitted to each proband by his/her parents (the haplotype relative risk method); (ii) cord blood samples from African-American neonates born locally. Molecular genetic analysis will be conducted using published methods. If the preliminary associations are not detected, associations at other 'candidate gene' loci will be investigated. Though the probands will be ascertained using DSM IIIR criteria, associations based on other diagnostic schemes will also be tested. Thus, biologically meaningful associations may be detected. This will help identify disease susceptibility genes, which will be useful for identifying individuals at risk. This study is among the first of its kind among African- Americans - a hitherto neglected area of research. The applicant has received a Scientist Development Award for Clinicians (K20MH00966, Sept. '92 -Aug. '97, ADAMHA). He has obtained clinical and laboratory based training in genetic epidemiology. He is currently conducting genetic studies in schizophrenia.